Phenol ether of quinin carbonic acid.



UNITED STATES PATENT OFFICE.

ALBERT WELLER, OF' FRANKFORT-ON-THE-MAIN, GERMANY, ASSIGNOR TOVERETNIGTE CHININFABRIKEN, ZIMMER d: 00., GESELLSOHAFT MIT BF-SGHRANKTER HAFTUNG, OF SAME PLACE.

P HENOL ETHER OF'QUININ CARBONIC ACID.

SPECIFICATION forming part of Letters Patent NO. 646,631, dated April 3,1900. Application filed November 18, 1899. Serial No. 737,501. (Nospecimens.)

To all whom it may concern:

Be it known that I, ALBERT WELLER, a subject of the Em er'or of German 7and a es'- v 1 p r 1 .in the preparation of, say, the phenoletherof dentof Frankfort-on-the-Main, Germany,

have invented certain new and useful Im-- tained I showed thepreparation of pharmaceutical products, being derivatives-of thealkaloids of cinchona bark, having, when quinin is used, the followinggeneral formula:

ao/ zo ss z z a: representing a single haloid atom or an alkyloxy group.

I have now succeeded in obtaining a series of further bodies which arealso derivatives of the cinchona alkaloids and which when quinin isemployed may be derived from the formula above stated, viz:

0c signifying, instead of an alkyloxy group, as methyloxyl (O.OHethyloxyl (OO H benzyloxyl (OOH O H or the like, the residue ofaphenol-as, for instance, carbolic acid, paranitrophenol, thymol,pyrocatechin. These new preparations, being phenolethers of the quinincarbonic acid or the carbonic acids .of other cinchona alkaloids, areall white tasteless crystals, whichvery readily dissolve in alcohol andchloroform, but with difficulty in water. The preparation may take placeaccording to the method described in Patent No. 585,068 by causingphenolethers of chlorocarbonic acid as such or dissolved in a suit ablesolvent to act upon quinin or another cinchona alkaloid, which may ormay not be anhydrous and may be either dissolved or suspended in asuit-able medium, but, instead of the pure alkaloids a salt of thealkaloids, as sulfate or muriate, may also be used.

The following directions may be observed quinin carbonic acid: Fivekilograms of quinin, forty kilograms of benzene, and 1.5 kilograms ofchlorocarbonic phenolether are boiled together for some while. The reac=tion takes place according to the following equation:

The mixture is then allowed to stand for sev= eral hours. Then themuriate of quinin is filtered, the benzene solution is agitated withwater and'then with diluted acid, which latter eliminates thephenolether of quinin carbonic acidfrom the benzene solution. Byaddition of an alkali to the acid solution the phenolether mayprecipitated and then crystallized out of a mixtureof a sulfuric etherand ligroin. The phenolether of quinin car bonic acid forms fine whitecrystals having their point of fusion at 129 centigrade and dissolvingwith great difficulty in water and ligroin, but readilyin alcohol,ether, and chloroform. The analysis gave:

Calculated for CO Found.

oc,H,. I o 72.97% 73.12% H: 6.30% 6.16%

The phenolether of quinin carbonic acid has basic properties formingcrystallizing salts with acids.

cess of the carbonate.

trophenolether of quinin carbonic acid is distake an excess of thephenolether in question. With the univalentphenols the reaction takesplace according to the following scheme:

I. Preparation of quinin carbonic phenolcthcr.lqnal weights of qnininand phenol carbonate are heated in an oil-bath at 120 to 130 centigradeuntil the melt no longer tastes bitter. While still warm the reactionmixture is dissolved in benzene, the qninin carbonic phenoletherproduced being then taken up by sulfuric or some other diluted acid andprecipitated with alkali. It can be purified by recrystallization-forexample, from ether and ligroin. The compound is identicalwith theabove-mentioned phenolether of .quinin carbonic acid prepared byactionof chlorocarbonic phenol other on quinin.

II. Preparation of quinin carbonic paranitrophcnol (alien-Equal weightsof quinin and paranitrophenol carbonate are heated together, asdescribed above in the first example; but it is useful to take a greaterex- The formed paranisolved in benzene, taken up by a diluted acid, andprecipitated with alkali. It crystallizes f-otleth-.l 1r" 'l'tttl.

m e em so n e as 6658 be obtained. This solution 1s drled byaddcrystals, having the formula and dissolving readily in alcohol,benzene, and chloroform, but with difficulty in ether. 2 The I meltingat 186 centigrade.

the salicylate gave the following result;

They are melted at 187 centigrade. analysis gave:

Calculated for O., .H ,.N;,O Found.

The body has basic properties and forms salts. The sulfate is difiicultto dissolve in alcohol. The solution in sulfuric acid shows a greenfluorescence.

III. Preparation of quinin carbonic paracefyl cmnidophcnolethcr.It canbe prepared, as described above,by melting quinin with an excess ofparacetyl amidophenol carbonate; but it is better obtained by boilingequal parts of .quinin and the said carbonate with xylene during tenhours on the reflux-cooler. From the xylene solution thus obtained theformed ether is separated, as above stated in example I. It can bepurified by converting it into the salicylate. For this purpose to theethereal solution salicylic acid is added until no more precipitate isobtained. The salicylate formed is crystallized out of alcohol. It formswhite crystals having their point of fusion at 174 centigrade anddissolving with great difficulty in water and sulfuric ether,

by ligroin.

being likewise diflicult to dissolve in cold alcohol, but readily in hotalcohol. The analysis of the salicylate led to the following re- Snlt:

Calculated for CMHMNQO, Found.

By shaking the salicylate with ether and diluted' alkali and evaporatingthe ethereal solution the free paraacetylamidophenolether of qninincarbonic acid can be obtained. Crystallized out of diluted alcohol itforms white tasteless crystals having the formula /OOGH4N n. 0,1 1. 0

t s t ethereal solution of the quinin .carbonicthymolether and is thencrystallized outof alcohol. It forms white crystals, melting at 172centigrade,'being readily soluble in alcohol, but dissolving with greatdifiiculty in water and ether. By agitating the salicylate with etherand diluted alkali an ethereal solution of the free quinin carbonicthymol ether can ing chlorid of calcium, and then the thymol ether ofquinin carbonic acid is precipitated This body has the formula uan andcrystallizes in white tasteless crystals,

Calculated for C. ,,.H .N .O Found.

V. Preparation of quinz'n carbonic pyrocctechaZether.The process iscarried .out exactly as in the case 1, above given, according to theequation:

rates is recrystallized from dilute alcohol. The sulfate forms whiteneedles, dissolving The analysis of I with difficulty in alcohol, butreadily in Water. Analysis gave Calculated for O27H2BN2O5.H2SO4. Found.

N 5.02% 5.3% l-i so, 21.30% 21.29%

I claim The new pharmaceutical products being derivatives of thealkaloids of the cinchona bark forming tasteless white crystals, veryreadily soluble in alcohol and chloroform but with difficulty in water,and having, when quinin is used the general formula 0c representing aphenyloxy group, substantially as and for the purpose set forth.

In testimony whereof I have signed my name to this specification in thepresence of two subscribing witnesses.

ALBERT WELLER.

Witnesses:

JEAN GRUND, SIMON W. HANAUER.

